Autoimmune uveitis: risk factors and issues of immunopathogenesis
We present recent advances in studying the mechanisms of susceptibility to immune-mediated uveitis (IM) and its pathogenesis. Animal models of human uveitis are described in details. Those include the best characterized models of experimental anterior uveitis (endotoxin-induced uveitis and experimen...
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St. Petersburg branch of the Russian Association of Allergologists and Clinical Immunologists
2025-01-01
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| Series: | Медицинская иммунология |
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| Online Access: | https://www.mimmun.ru/mimmun/article/view/2956 |
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| author | I. V. Shirinsky V. S. Shirinsky |
| author_facet | I. V. Shirinsky V. S. Shirinsky |
| author_sort | I. V. Shirinsky |
| collection | DOAJ |
| description | We present recent advances in studying the mechanisms of susceptibility to immune-mediated uveitis (IM) and its pathogenesis. Animal models of human uveitis are described in details. Those include the best characterized models of experimental anterior uveitis (endotoxin-induced uveitis and experimental autoimmune anterior uveitis). As a result of these studies, some relevant transcription factors were detected, such as STAT3, Interferon regulatory factor 4, 8; regulatory proteins, e.g., suppressors of cytokine signaling 1, 3 (SOCS1, SOCS3) and cytokine signaling pathways that regulate the development of IS and may serve as potential therapeutic targets for treatment. Environmental risk factors contributing to the development of IS are also characterized. The presented data concern the influence of physical activity, smoking, state of intestinal microbiome, and diet on the incidence of IS, as well as known and suspected contribution of the risk factors to the initiation and pathogenesis of the disease. In particular, we present results of studies which suggest two main options of intestinal microbiome involvement in the IS development: intestinal microbiome antigens act as triggers for activation of T cells specific for retinal antigens, and the microbiome modulates the balance of effector subpopulations of T lymphocytes (Th1 and Th17) and immunoregulatory subpopulations cells (Treg). It is reported that high levels of expression of ocular proteins (interphotoreceptor retinoid binding protein – IRBP or S-antigen) in the thymus correlated with resistance to the development of EAU, while low IRBP levels correlated with susceptibility to uveitis. These seminal studies in pathogenesis of IU allowed explanation for selective susceptibility to autoimmune uveitis and suggested regulation tools of resistance to uveitis, at least, in part, due to ability of maintaining central tolerance to retinal autoantigens. Uveitogenic memory T cells have been described to move from retina and peripheral lymphoid tissues to the bone marrow, remaining there in a quiescent state until re-stimulation, then transforming into various subpopulations of effector cells. Analysis of immunological studies in murine models of uveitis and peripheral blood of patients with uveitis had revealed a pathogenetic role of Th17 lymphocytes and a transcription activator STAT3 in development of autoimmune uveitis, with STAT3 signaling protein being a potential therapeutic target for non-infectious uveitis. |
| format | Article |
| id | doaj-art-a16d84696c2b4946965b209496d1e991 |
| institution | Kabale University |
| issn | 1563-0625 2313-741X |
| language | Russian |
| publishDate | 2025-01-01 |
| publisher | St. Petersburg branch of the Russian Association of Allergologists and Clinical Immunologists |
| record_format | Article |
| series | Медицинская иммунология |
| spelling | doaj-art-a16d84696c2b4946965b209496d1e9912025-08-20T04:00:26ZrusSt. Petersburg branch of the Russian Association of Allergologists and Clinical ImmunologistsМедицинская иммунология1563-06252313-741X2025-01-0127172010.15789/1563-0625-AUR-29561885Autoimmune uveitis: risk factors and issues of immunopathogenesisI. V. Shirinsky0V. S. Shirinsky1Research Institute of Internal and Preventive Medicine, Branch of the Institute of Cytology and Genetics, Siberian Branch, Russian Academy of SciencesResearch Institute of Internal and Preventive Medicine, Branch of the Institute of Cytology and Genetics, Siberian Branch, Russian Academy of SciencesWe present recent advances in studying the mechanisms of susceptibility to immune-mediated uveitis (IM) and its pathogenesis. Animal models of human uveitis are described in details. Those include the best characterized models of experimental anterior uveitis (endotoxin-induced uveitis and experimental autoimmune anterior uveitis). As a result of these studies, some relevant transcription factors were detected, such as STAT3, Interferon regulatory factor 4, 8; regulatory proteins, e.g., suppressors of cytokine signaling 1, 3 (SOCS1, SOCS3) and cytokine signaling pathways that regulate the development of IS and may serve as potential therapeutic targets for treatment. Environmental risk factors contributing to the development of IS are also characterized. The presented data concern the influence of physical activity, smoking, state of intestinal microbiome, and diet on the incidence of IS, as well as known and suspected contribution of the risk factors to the initiation and pathogenesis of the disease. In particular, we present results of studies which suggest two main options of intestinal microbiome involvement in the IS development: intestinal microbiome antigens act as triggers for activation of T cells specific for retinal antigens, and the microbiome modulates the balance of effector subpopulations of T lymphocytes (Th1 and Th17) and immunoregulatory subpopulations cells (Treg). It is reported that high levels of expression of ocular proteins (interphotoreceptor retinoid binding protein – IRBP or S-antigen) in the thymus correlated with resistance to the development of EAU, while low IRBP levels correlated with susceptibility to uveitis. These seminal studies in pathogenesis of IU allowed explanation for selective susceptibility to autoimmune uveitis and suggested regulation tools of resistance to uveitis, at least, in part, due to ability of maintaining central tolerance to retinal autoantigens. Uveitogenic memory T cells have been described to move from retina and peripheral lymphoid tissues to the bone marrow, remaining there in a quiescent state until re-stimulation, then transforming into various subpopulations of effector cells. Analysis of immunological studies in murine models of uveitis and peripheral blood of patients with uveitis had revealed a pathogenetic role of Th17 lymphocytes and a transcription activator STAT3 in development of autoimmune uveitis, with STAT3 signaling protein being a potential therapeutic target for non-infectious uveitis.https://www.mimmun.ru/mimmun/article/view/2956immune-mediated uveitis, experimental models of non-infectious uveitis, risk factors for uveitis, central and peripheral tolerance, t helper cells, th17 lymphocytes, stat3 signaling protein |
| spellingShingle | I. V. Shirinsky V. S. Shirinsky Autoimmune uveitis: risk factors and issues of immunopathogenesis Медицинская иммунология immune-mediated uveitis, experimental models of non-infectious uveitis, risk factors for uveitis, central and peripheral tolerance, t helper cells, th17 lymphocytes, stat3 signaling protein |
| title | Autoimmune uveitis: risk factors and issues of immunopathogenesis |
| title_full | Autoimmune uveitis: risk factors and issues of immunopathogenesis |
| title_fullStr | Autoimmune uveitis: risk factors and issues of immunopathogenesis |
| title_full_unstemmed | Autoimmune uveitis: risk factors and issues of immunopathogenesis |
| title_short | Autoimmune uveitis: risk factors and issues of immunopathogenesis |
| title_sort | autoimmune uveitis risk factors and issues of immunopathogenesis |
| topic | immune-mediated uveitis, experimental models of non-infectious uveitis, risk factors for uveitis, central and peripheral tolerance, t helper cells, th17 lymphocytes, stat3 signaling protein |
| url | https://www.mimmun.ru/mimmun/article/view/2956 |
| work_keys_str_mv | AT ivshirinsky autoimmuneuveitisriskfactorsandissuesofimmunopathogenesis AT vsshirinsky autoimmuneuveitisriskfactorsandissuesofimmunopathogenesis |